Contact Information
Research Interests
Cell-cell signaling during hypothalamic neuron development and pituitary development
Impact of endocrine disrupting chemicals during gestation on hypothalamic-pituitary development
Research Description
The hypothalamus is a critical center for homeostasis in the body and is essential for feeding, growth and reproduction, among other things. The neuroendocrine hypothalamus arises from progenitors lining the third ventricle of the brain. Obesity, infertility and dwarfism can be linked to aberrant development of these neurons. Despite the importance of this brain region to normal physiology, little is known about the factors that are necessary to get the wide variety of peptide producing neurons.
We have a focus on the Notch signaling pathway, which we hypothesize plays an important role in the proliferation and lineage specific differentiation of hypothalamic progenitor cells. We are exploring if Notch signaling is necessary and sufficient for obtaining the full complement of cells in the Arcuate Nucleus of the hypothalamus by employing transgenic and knockout mice. These studies also take advantage of molecular genetic techniques and whole animal physiology. We have an exciting collaboration with the Underhill lab that involves isolating hypothalamic stem cells and culturing them on engineered arrays so that we can test a wide variety of tethered and secreted stimuli that may influence neuron development. We are also interested in how maternal environment, including obesity or exposure to endocrine disrupting chemicals can impact hypothalamic progenitors.
The overall goal of these studies is to define the normal complement of signals that stem cells use to make fate choices in the hypothalamus. This information will be useful in finding causes for congenital neuroendocrine disorders. It also may be possible to someday engineer new neurons to replace those that don’t develop correctly or those that are damaged by brain injury
Education
B.A. Ripon College
Ph.D. Case Western Reserve University
Awards and Honors
Faculty Recognition Award, Neuroscience Student Organization
Outstanding Advisor Award, Medical Scholars Program
Additional Campus Affiliations
Molecular and Integrative Physiology
Affiliate, Neuroscience Program
Affiliate, Institute for Genomic Biology
External Links
Honors & Awards
Medical Scholars Program Outstanding Advisor Award (2015)
James Heath Award for Excellence in Teaching (2010)
Recent Publications
Barbosa, K. L., Dettogni, R. S., Da Costa, C. S., Gastal, E. L., Raetzman, L. T., Flaws, J. A., & Graceli, J. B. (2022). Tributyltin and the Female Hypothalamic-Pituitary-Gonadal Disruption. Toxicological Sciences, 186(2), 179-189. https://doi.org/10.1093/toxsci/kfab141
Cutia, C. A., Leverton, L. K., Ge, X., Youssef, R., Raetzman, L. T., & Christian-Hinman, C. A. (2022). Phenotypic differences based on lateralization of intrahippocampal kainic acid injection in female mice. Experimental Neurology, 355, [114118]. https://doi.org/10.1016/j.expneurol.2022.114118
Ge, X., Weis, K., Flaws, J., & Raetzman, L. (2022). Prenatal exposure to the phthalate DEHP impacts reproduction-related gene expression in the pituitary. Reproductive Toxicology, 108, 18-27. https://doi.org/10.1016/j.reprotox.2021.12.008
Gonzalez, R. V. L., Weis, K. E., Gonsioroski, A. V., Flaws, J. A., & Raetzman, L. T. (2021). Iodoacetic Acid, a Water Disinfection Byproduct, Disrupts Hypothalamic and Pituitary Reproductive Regulatory Factors and Induces Toxicity in the Female Pituitary. Toxicological sciences : an official journal of the Society of Toxicology, 184(1), 46-56. https://doi.org/10.1093/toxsci/kfab106
Weis, K. E., & Raetzman, L. T. (2019). Genistein inhibits proliferation and induces senescence in neonatal mouse pituitary gland explant cultures. Toxicology, 427, [152306]. https://doi.org/10.1016/j.tox.2019.152306